In vitro biological properties of pyridoxine and ketorolac conjugates.

Prodrugs based on pyridoxine and ketorolac (the most potent analgesic NSAIDs) exhibit analgesic activity comparable to ketorolac in vivo and significantly higher safety and prolonged action. In this study the antioxidant and protective properties, inhibitory activity against cyclooxygenase (COX) and intracellular permeability for two prodrug bipharmacophoric conjugates based on pyridoxine and ketorolac have been investigated in vitro. Their inhibitory activity towards the COX-1 and COX-2 enzymes was comparable to that of ketorolac (the IC50 values ranged from 12.0 μM to 34.7 μM). These compounds markedly protected albumin against thermal and chemical (urea and citric acid) treatments and demonstrated the cell-penetrating ability through passive diffusion.